Recent experiments in our laboratory have confirmed the observation that during the first 28 days after birth the neonatal rat undergoes a remarkable pattern of activity which Campbell and associates have termed the development of behavioral arousal. For the first 8-10 days of life the rat pup moves very little. However at approximately 12-16 days of age his spontaneous activity begins to increase, reaches its peak during the third week of life and then declines to the level it was prior to the increase, to remain stable until it declines again in senescence. Several lines of evidence suggest that the development of behavioral excitability found in the 2-3 week old rat pup is mediated via catecholaminergic mechanisms. We propose to examine the relationship between brain catecholamines (norepinephrine and dopamine) and behavioral states by utilizing the agent 6-hydroxydopamine. This compound has provided investigators with a powerful new method to pharmacologically deplete brain norepinephrine or dopamine selectively in order to elucidate the role of each catecholamine on the ontogeny of behavioral arousal. Behavior will also be examined in the developing rats after administration of amphetamine, an agent whose central actions are believed mediated by catecholamines. The effect of amphetamine has not been examined in developing animals and it is possible that such an investigation may provide insight into the so-called paradoxical effects of amphetamines on young children with the syndrome of minimal brain dysfunction (MBD). In addition, the effect of perinatal anoxia on both brain amines and behavior will be investigated. This insult is believed to be related to the subsequent development of MBD in children and recent evidence indicates that anoxia affects brain amines as well. It will be of great interest to determine whether anoxia in the perinatal period does indeed affect behavior in the developing rat as well as whether anoxia will affect brain catecholamines. BIBLIOGRAPHIC REFERENCE: Shaywitz, B.A., Yager, R.D., and Klopper, J.H.: Selective Brain Dopamine Depletion in Developing Rats: An Experimental Model of Minimal Brain Dysfunction. Science 191: 305-308, 1976.